Inflammation is commonly divided into three phases: acute inflammation, the immune response and chronic inflammation. Acute inflammation is the initial response to tissue injury and is mediated by the release of histamine, serotonin, bradykinin, prostaglandins and leukotrienes. The immune response, usually preceded by the acute inflammation phase, occurs when immunologically competent cells are activated in response to foreign organisms or antigenic substances liberated during the acute or chronic inflammatory response. The outcome of the immune response for the host may be beneficial, as when it causes invading organisms to be phagocytosed or neutralized. However, the outcome may be deleterious if it leads to chronic inflammation without resolution of the underlying injurious process as it occurs in rheumatoid arthritis.
The treatment of patients with inflammation envisages the relief of pain, which is the presenting symptom and the major continuing complaint of the patient, as well as the slowing or arrest of the tissue-damaging process.
Anti-inflammatory agents are usually classified as steroidal or glucocorticoids and nonsteroidal anti-inflammatory agents (NSAIDs). The glucocorticoids are powerful anti-inflammatory agents but the high toxicity associated with chronic corticosteroid therapy inhibits their use except in certain acute inflammatory conditions. Although NSAIDs have assumed a major role in the treatment of chronic conditions such as rheumatoid arthritis, they are also associated with various toxicities ranging from gastrointestinal bleeding to life-threatening cardiotoxicity.
PCT application publication number WO 02/083122, hereby incorporated by reference, discloses fatty alcohols and fatty esters useful for treating inflammation. PCT application publication number WO 02/083059, hereby incorporated by reference, discloses uses of esters of long-chained fatty acids for the treatment of autoimmune diseases and other immune-associated inflammatory disorders.
What is needed are novel compounds for treating inflammation that are less toxic to the patient.